dose escalating study of foxy-5 in breast-, colon- or prostate cancer patients

Conditions: Metastatic Breast Cancer; Metastatic Colon Cancer; Metastatic Prostate Cancer

Summary: the wnt proteins belong to a family of proteins that have been demonstrated to play a role in the formation and dissemination of tumours. the present project focuses on the critical role of the wnt-5a protein in the pathobiological processes that lead to metastatic cancer disease. wntresearch has identified a formylated 6 amino acid peptide fragment, named foxy-5, which mimick the effects of wnt-5a to impair migration of epithelial cancer cells and thereby acting anti-metastatic. the aim of the first clinical phase i study was to establish the recommended dose for a clinical phase ii study and enable further development of foxy-5 as a first in class anti-metastatic cancer drug. the study did not see any dlts and therefore failed to reach maximum tolerated dose (mtd); no recommended phase ii dose (rp2d) could therefore be established based on toxicity. the aim of this study is to continue to establish the safety profile of foxy-5 in higher doses, and determine the rp2d for later stage development based on any observed dlt's/mtd and further analysis of the pharmacodynamic profile of foxy-5 to determine the biological response dose (brd).


Eligibility criteria:
inclusion criteria: * males and females of at least 18 years of age * histologically/cytologically documented diagnosis of metastatic breast, colon or prostate cancer, refractory to standard therapy or for which no curative therapy exists * must have an evaluable tumour appropriate for biopsy as determined by the investigator. * loss of or reduced wnt-5a protein expression in primary or metastatic tumour cells, characterised by ihc analysis * eastern cooperative oncology group (ecog) performance status of \<= 1 * life expectancy of at least 3 months * unresectable disease, i.e. the metastases cannot be surgically removed with a curative intent * 4 weeks must have elapsed since the patient has received any other imp * 4 weeks must have elapsed since the patient has received any anti cancer treatment; including radiotherapy (except for single dose of palliative radiotherapy), cytotoxic chemotherapy, biologic agents or targeted therapy * 2 weeks must have elapsed since any prior surgery or therapy with bone marrow stimulating factors * adequate haematological functions as defined by: * absolute neutrophil count \>= 1.5 10e9/l * platelets \>= 100 10e9/l * hemoglobin \>= 5.6 mmol/l * adequate hepatic function as defined by: * total bilirubin \<= 1.5 x the upper limit of normal (uln) * aspartate aminotransferase (ast) \<= 2.5 x uln\* * alanine aminotransferase (alt) \<= 2.5 x uln\* * for patients with liver metastasis adequate hepatic function is defined by ast \<= 5 x uln and alt \<= 5 uln. * adequate renal function as defined by serum creatinine \<= 1,5 x uln * patients in active anti-coagulating treatment must be evaluated according to local standards on the discretion of the investigator.. * provision of written informed consent * willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures * sexually active males and females of child-producing potential, must use adequate contraception (intrauterine devices, hormonal contraceptives (contraceptive pills, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release) or diaphragm always with spermicidal jelly and a male condom) for the study duration and at least six months afterwards exclusion criteria: * active uncontrolled bleeding or bleeding diathesis (e.g., active peptic ulcer disease) * any active infection requiring antibiotic treatment * known infection with human immunodeficiency virus (hiv) or hepatitis virus * active heart disease including myocardial infarction or congestive heart failure within the previous 6 months, symptomatic coronary artery disease, or symptomatic arrhythmias currently requiring medication * known or suspected active central nervous system (cns) metastasis. (patients stable 8 weeks after completion of treatment for cns metastasis are eligible) * impending or symptomatic spinal cord compression or carcinomatous meningitis * requiring immediate palliative surgery and/or radiotherapy(except for a single dose of palliative radiotherapy) * pre-existing neuropathy, i.e., grade \>2 neuromotor or neurosensory toxicity * participation in other clinical studies within 4 weeks of first dose of study treatment * previous exposure to foxy-5 * history of severe allergic or hypersensitive reactions to excipients * pregnant or breastfeeding women * active and/or within the last 5 years histologically confirmed diagnosis of malignant melanoma, gastric cancer, pancreatic cancer, lung cancer or nasopharyngeal cancer * severe or uncontrolled chronic or uncontrolled systemic disease (e. g. severe respiratory or cardiovascular disease) * other medications or conditions that in the investigator's opinion would contraindicate study participation of safety reasons or interfere with the interpretation of study results